Thromb Haemost 2022; 122(11): 1899-1910
DOI: 10.1055/a-1807-0336
Stroke, Systemic or Venous Thromboembolism

Early Rhythm Control and the Risks of Ischemic Stroke, Heart Failure, Mortality, and Adverse Events When Performed Early (<3 Months): A Nationwide Cohort Study of Newly Diagnosed Patients with Atrial Fibrillation

Tze-Fan Chao*
1   Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
2   Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
3   Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
,
Yi-Hsin Chan*
4   The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
5   College of Medicine, Chang Gung University, Taoyuan, Taiwan
6   Microscopy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
,
Chern-En Chiang
1   Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
2   Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
3   Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
7   General Clinical Research Center, Taipei Veterans General Hospital, Taipei, Taiwan
,
Ta-Chuan Tuan
1   Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
2   Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
3   Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
,
Jo-Nan Liao
1   Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
2   Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
3   Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
,
Tzeng-Ji Chen
8   Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
,
Gregory Y. H. Lip***
9   Liverpool Centre for Cardiovascular Science, University of Liverpool & Liverpool Heart and Chest Hospital, Liverpool, United Kingdom
10   Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark, United Kingdom
,
Shih-Ann Chen**
1   Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
2   Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
3   Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
11   Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan
› Author Affiliations
Funding This work was supported in part by grants from the Ministry of Science and Technology (MOST 107-2314-B-075-062-MY3), Taipei Veterans General Hospital (V108B-015, V108B-027, V108C-090, V109C-042, V109C-186), Research Foundation of Cardiovascular Medicine, and Szu-Yuan Research Foundation of Internal Medicine, Taipei, Taiwan.


Abstract

Background In the Early Treatment of Atrial Fibrillation for Stroke Prevention Trial (EAST-AFNET 4), early rhythm control was associated with better clinical outcomes for patients with atrial fibrillation (AF). However, the intervention arm had more structured and regular follow-up, and whether the better outcomes of patients assigned to rhythm control were solely due to “early” intervention or because of more regular and structured follow-up was unclear.

Objective In the present study, we aimed to investigate whether the findings of the EAST trial are applicable to the “real-world” clinical setting, where a less structured management protocol is operated.

Methods From 2001 to 2016, 301,064 newly diagnosed AF patients were identified from Taiwan National Health Insurance Research Database. Among these patients, 62,649 AF patients receiving antiarrhythmic drugs or catheter ablation within 1 year after AF being diagnosed (similar to the timing definition of the EAST-AFNET 4 trial) were categorized as the early rhythm control group, and the remaining 238,415 patients were defined as usual care group. Risks of clinical events were compared between the two groups.

Results Compared with usual care, early rhythm control was associated with a lower adjusted risk of ischemic stroke (adjusted hazard ratio [aHR]: 0.771, 95% confidence interval [CI]: 0.751–0.792; p < 0.001), heart failure (aHR: 0.851, 95% CI: 0.806–0.899; p < 0.001), acute myocardial infarction (aHR: 0.915, 95% CI: 0.877–0.955; p < 0.001), mortality (aHR: 0.794, 95% CI: 0.782–0.806; p < 0.001), and composite adverse events (aHR: 0.823, 95% CI: 0.813–0.834; p < 0.001). Compared with usual care, the lower risks of ischemic stroke (aHR: 0.746, 95% CI: 0.717–0.775), heart failure (aHR: 0.819, 95% CI: 0.798–0.841), mortality (aHR: 0.777, 95% CI: 0.759–0.795), and composite adverse events (aHR: 0.802, 95% CI: 0.787–0.818) associated with early rhythm control were even more evident when performed early (<3 months) compared to later periods (3–6 months, 7–9 months, and 10–12 months; p int < 0.001). Principal results were generally consistent for majority of subgroups studied and among the cohort after propensity matching.

Conclusion In this nationwide cohort study, early rhythm control therapy was associated with a lower risk of adverse events compared with usual care among patients with early AF. Outcomes were even better with earlier (<3 months) intervention.

* Drs. Chao and Chan contribute equally to this work and are joint first authors.


** Joint senior authors.


Note: The review process for this paper was fully handled by Christian Weber, Editor-in-Chief.


Author Contributions

Study concept and design: T.-F.C., G.Y.H.L., S.-A.C. Acquisition of data: T.-J.C., Y.-H.C. Analysis and interpretation of data: T.-F.C., C.-E.C., G.Y.H.L., S.-A.C. Drafting of the manuscript: T.-F.C., G.Y.H.L. Critical revision of the manuscript for important intellectual content: G.Y.H.L., S.-A.C. Statistical analysis: T.-F.C., T.-C.T., J.-N.L. Study supervision: G.Y.H.L., S.-A.C.


Note

This study is based on data from the Health and Welfare Data Science Center (HWDC), Ministry of Health and Welfare (MOHW), Taiwan. The interpretation and conclusions contained herein do not represent those of HWDC, MOHW, Taiwan.


Supplementary Material



Publication History

Received: 21 March 2022

Accepted: 22 March 2022

Accepted Manuscript online:
23 March 2022

Article published online:
30 July 2022

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